Cytohesin-4/ARF6 facilitates the progression of acute myeloid leukemia through activating PIK3R5/PI3K/AKT pathway
Summary: In silico analysis revealed an elevated expression of cytohesin-4 (CYTH4) in acute myeloid leukemia (AML) cells, correlating with a poorer prognosis for AML patients. However, its role in AML is not fully understood. Our study using loss-of-function assays identified CYTH4 as an oncogene pr...
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Elsevier
2025-06-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225008958 |
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| author | Xiao-Fen Qiu Cheng-Ming He Yan-Mei Zeng Xiao-Ling Deng Guo-Lin Liang Ming-Xing Zhong Min Zou Xiu-Juan Xiong Jing-Dong Zhang Yan Ye Qing Niu Xiao-Li Chen |
| author_facet | Xiao-Fen Qiu Cheng-Ming He Yan-Mei Zeng Xiao-Ling Deng Guo-Lin Liang Ming-Xing Zhong Min Zou Xiu-Juan Xiong Jing-Dong Zhang Yan Ye Qing Niu Xiao-Li Chen |
| author_sort | Xiao-Fen Qiu |
| collection | DOAJ |
| description | Summary: In silico analysis revealed an elevated expression of cytohesin-4 (CYTH4) in acute myeloid leukemia (AML) cells, correlating with a poorer prognosis for AML patients. However, its role in AML is not fully understood. Our study using loss-of-function assays identified CYTH4 as an oncogene promoting leukemogenesis. Silencing CYTH4 in MV4-11 and THP-1 cells reduced cell proliferation and colony formation, and induced apoptosis and cell-cycle arrest at G0/G1, whereas overexpression had no significant impact. CYTH4 silencing also increased chemosensitivity to cytarabine. In a THP-1 xenograft model, CYTH4 silencing slowed AML progression and reduced leukemic cell homing and infiltration. Mechanistically, CYTH4 silencing inhibited PI3K/AKT pathway by lowering PIK3R5 and decreased ARF6-GTP levels, as confirmed by pull-down assays. Overexpression of PIK3R5 and AKT activation via SC-79 successfully countered the cellular dysfunctions from CYTH4 silencing. Thus, CYTH4 may play a role in AML progression, and targeting its pathway could be a promising anti-leukemic treatment strategy. |
| format | Article |
| id | doaj-art-c4dd3f715d314674b5937e9dba57d417 |
| institution | OA Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-c4dd3f715d314674b5937e9dba57d4172025-08-20T01:52:55ZengElsevieriScience2589-00422025-06-0128611263410.1016/j.isci.2025.112634Cytohesin-4/ARF6 facilitates the progression of acute myeloid leukemia through activating PIK3R5/PI3K/AKT pathwayXiao-Fen Qiu0Cheng-Ming He1Yan-Mei Zeng2Xiao-Ling Deng3Guo-Lin Liang4Ming-Xing Zhong5Min Zou6Xiu-Juan Xiong7Jing-Dong Zhang8Yan Ye9Qing Niu10Xiao-Li Chen11Jiangxi Health Commission Key Laboratory of Leukemia, the Affiliated Ganzhou Hospital, Jiangxi Medical College, Nanchang University, Ganzhou 341000, China; Ganzhou Key Laboratory of Molecular Medicine, the Affiliated Ganzhou Hospital, Jiangxi Medical College, Nanchang University, Ganzhou 341000, ChinaJiangxi Health Commission Key Laboratory of Leukemia, the Affiliated Ganzhou Hospital, Jiangxi Medical College, Nanchang University, Ganzhou 341000, ChinaJiangxi Health Commission Key Laboratory of Leukemia, the Affiliated Ganzhou Hospital, Jiangxi Medical College, Nanchang University, Ganzhou 341000, China; Ganzhou Key Laboratory of Molecular Medicine, the Affiliated Ganzhou Hospital, Jiangxi Medical College, Nanchang University, Ganzhou 341000, ChinaJiangxi Health Commission Key Laboratory of Leukemia, the Affiliated Ganzhou Hospital, Jiangxi Medical College, Nanchang University, Ganzhou 341000, China; Ganzhou Key Laboratory of Molecular Medicine, the Affiliated Ganzhou Hospital, Jiangxi Medical College, Nanchang University, Ganzhou 341000, ChinaJiangxi Health Commission Key Laboratory of Leukemia, the Affiliated Ganzhou Hospital, Jiangxi Medical College, Nanchang University, Ganzhou 341000, China; Ganzhou Key Laboratory of Molecular Medicine, the Affiliated Ganzhou Hospital, Jiangxi Medical College, Nanchang University, Ganzhou 341000, ChinaJiangxi Health Commission Key Laboratory of Leukemia, the Affiliated Ganzhou Hospital, Jiangxi Medical College, Nanchang University, Ganzhou 341000, ChinaJiangxi Health Commission Key Laboratory of Leukemia, the Affiliated Ganzhou Hospital, Jiangxi Medical College, Nanchang University, Ganzhou 341000, ChinaDepartment of Pathology, Jiangxi Medical College, Nanchang University, Nanchang 330031, ChinaJiangxi Health Commission Key Laboratory of Leukemia, the Affiliated Ganzhou Hospital, Jiangxi Medical College, Nanchang University, Ganzhou 341000, ChinaJiangxi Health Commission Key Laboratory of Leukemia, the Affiliated Ganzhou Hospital, Jiangxi Medical College, Nanchang University, Ganzhou 341000, China; Ganzhou Key Laboratory of Molecular Medicine, the Affiliated Ganzhou Hospital, Jiangxi Medical College, Nanchang University, Ganzhou 341000, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, ChinaJiangxi Health Commission Key Laboratory of Leukemia, the Affiliated Ganzhou Hospital, Jiangxi Medical College, Nanchang University, Ganzhou 341000, China; Ganzhou Key Laboratory of Molecular Medicine, the Affiliated Ganzhou Hospital, Jiangxi Medical College, Nanchang University, Ganzhou 341000, China; Corresponding authorSummary: In silico analysis revealed an elevated expression of cytohesin-4 (CYTH4) in acute myeloid leukemia (AML) cells, correlating with a poorer prognosis for AML patients. However, its role in AML is not fully understood. Our study using loss-of-function assays identified CYTH4 as an oncogene promoting leukemogenesis. Silencing CYTH4 in MV4-11 and THP-1 cells reduced cell proliferation and colony formation, and induced apoptosis and cell-cycle arrest at G0/G1, whereas overexpression had no significant impact. CYTH4 silencing also increased chemosensitivity to cytarabine. In a THP-1 xenograft model, CYTH4 silencing slowed AML progression and reduced leukemic cell homing and infiltration. Mechanistically, CYTH4 silencing inhibited PI3K/AKT pathway by lowering PIK3R5 and decreased ARF6-GTP levels, as confirmed by pull-down assays. Overexpression of PIK3R5 and AKT activation via SC-79 successfully countered the cellular dysfunctions from CYTH4 silencing. Thus, CYTH4 may play a role in AML progression, and targeting its pathway could be a promising anti-leukemic treatment strategy.http://www.sciencedirect.com/science/article/pii/S2589004225008958CancerCell biology |
| spellingShingle | Xiao-Fen Qiu Cheng-Ming He Yan-Mei Zeng Xiao-Ling Deng Guo-Lin Liang Ming-Xing Zhong Min Zou Xiu-Juan Xiong Jing-Dong Zhang Yan Ye Qing Niu Xiao-Li Chen Cytohesin-4/ARF6 facilitates the progression of acute myeloid leukemia through activating PIK3R5/PI3K/AKT pathway iScience Cancer Cell biology |
| title | Cytohesin-4/ARF6 facilitates the progression of acute myeloid leukemia through activating PIK3R5/PI3K/AKT pathway |
| title_full | Cytohesin-4/ARF6 facilitates the progression of acute myeloid leukemia through activating PIK3R5/PI3K/AKT pathway |
| title_fullStr | Cytohesin-4/ARF6 facilitates the progression of acute myeloid leukemia through activating PIK3R5/PI3K/AKT pathway |
| title_full_unstemmed | Cytohesin-4/ARF6 facilitates the progression of acute myeloid leukemia through activating PIK3R5/PI3K/AKT pathway |
| title_short | Cytohesin-4/ARF6 facilitates the progression of acute myeloid leukemia through activating PIK3R5/PI3K/AKT pathway |
| title_sort | cytohesin 4 arf6 facilitates the progression of acute myeloid leukemia through activating pik3r5 pi3k akt pathway |
| topic | Cancer Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225008958 |
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